Hoffa fractures are associated with concomitant soft tissue injures and a high postoperative complication rate.

INTRODUCTION: Hoffa fractures are a rare and often overlooked entity. The main goal of surgical treatment is to restore the articular surface and maintain knee function. However, current clinical data indicate heterogeneous outcomes. The aim of this multicenter study was to obtain a representative data set of patients with isolated Hoffa fractures with special emphasis on concomitant soft tissue injuries, diagnostic algorithms, treatment strategies and functional outcomes. MATERIALS AND METHODS: Participating Level I trauma centres were asked to review their internal database for isolated Hoffa fractures treated surgically between 2010 and 2020. Demographics, mechanism of injury, diagnostic and therapeutic algorithm, Letenneur classification, concomitant soft tissue injuries, and postoperative knee function and complications were analysed. RESULTS: A total of 56 patients from six participating trauma centres were included. The median age at injury was 45 years (15-94) with a median follow-up of 19 months (2-108). The most common mechanism of injury was high-energy trauma, with unicondylar lateral Letenneur type I and II fractures being the most common. Surgical treatment was independent of the type of fracture and included isolated screw fixation, combined plate and screw fixation and isolated plate osteosynthesis. Isolated screw fixation resulted in significantly better range of motion (ROM) values (p = 0.032), but the highest number of postoperative complications (n = 14/20, n.s.) compared to the other fixation techniques. The highest number of fixation failures requiring revision was observed in the plate and screw fixation group (n = 3/8, p = 0.008). Osteochondral flake fractures (n = 12/43, 27%) and lateral meniscus injuries (n = 5/49, 10%) were commonly seen in Hoffa fractures. CONCLUSIONS: Treatment of Hoffa fractures with screw fixation resulted in significantly better functional outcomes, probably due to less comminuted fractures. Concomitant cartilage, meniscal and ligamentous injuries are common and warrant preoperative recognition and management.

Primary stability of single-stage revision reconstruction of the anterior cruciate ligament in case of failure of dynamic intraligamentary stabilization depends on implant position during ACL repair.

INTRODUCTION: The object of this study was to evaluate the primary stability of tibial interference screw (IFS) fixation in single-stage revision surgery of the anterior cruciate ligament (ACL) in the case of recurrent instability after ACL repair with dynamic intraligamentary stabilization (DIS), dependent on the implant position during DIS. MATERIALS AND METHODS: Tibial aperture fixation in ACL reconstruction (ACL-R) was performed in a porcine knee model using an IFS. Native ACL-R was performed in the control group (n = 15). In the intervention groups DIS and subsequent implant removal were performed prior to single-stage revision ACL-R. A distance of 20 mm in group R-DIS1 (n = 15) and 5 mm in group R-DIS2 (n = 15) was left between the joint line and the implant during DIS. Specimens were mounted in a material-testing machine and load-to-failure was applied in a worst-case-scenario. RESULTS: Load to failure was 454 ± 111 N in the R-DIS1 group, 154 ± 71 N in the R-DIS2 group and 405 ± 105 N in the primary ACL-R group. Load-to-failure, stiffness and elongation of the group R-DIS2 were significantly inferior in comparison to R-DIS1 and ACL-R respectively (p < 0.001). No significant difference was found between load-to-failure, stiffness and elongation of R-DIS1 and the control group. CONCLUSION: Primary stability of tibial aperture fixation in single-stage revision ACL-R in case of recurrent instability after DIS depends on monobloc position during ACL repair. Primary stability is comparable to aperture fixation in primary ACL-R, if a bone stock of 20 mm is left between the monobloc and the tibial joint line during the initial procedure.

[Anterolateral stabilization using the modified Lemaire technique for ACL deficiency]. / Anterolaterale Stabilisierung mittels modifizierter Lemaire-Plastik bei insuffizientem vorderem Kreuzband.

OBJECTIVE: Treatment of persistent anterolateral knee instability. INDICATIONS: Subjective/objective (rotational) instability of the knee after anatomic anterior cruciate ligament (ACL) reconstruction. ACL re-rupture including special demands (e.g., high-performance athletes, hyperlaxity) RELATIVE CONTRAINDICATIONS: Osteoarthritis, additional instability of the knee, which should be treated independently; non-anatomic ACL reconstruction with persisting instability should be treated first with anatomic ACL reconstruction. ABSOLUTE CONTRAINDICATIONS: General contraindications for surgery (e. g. septic arthritis), acute irritation of the affected knee. SURGICAL TECHNIQUE: Supine position. Incision along the proximal lateral femoral epicondyle. Marking of the needed width and length of the iliotibial band (ITB) graft. Passing the ITB graft underneath the lateral collateral ligament. Find and mark the isometric point for fixation next to the lateral femoral epicondyle. Fixation of the ITB graft. Layered wound closure. POSTOPERATIVE MANAGEMENT: Knee brace for at least 6 weeks. Range of motion (RoM): from postoperative day 1: flexion-extension 90-0-0°; first 2 weeks after surgery: partial weight bearing (20 kg). RESULTS: An anterolateral extra-articular reconstruction may reduce a persistent anterolateral rotatory instability as well as the re-rupture rate following ACL reconstruction with good patient-reported short-term outcomes. Based on current (biomechanical) data, anterolateral tenodesis seems to be superior to a reconstruction of the anterolateral ligament. If a tenodesis is performed, the graft should be fixed in an isometric position, with neutral rotation of the knee and low graft tension to avoid extraphysiologic load within the lateral compartment. Indications for such a procedure may include a high-grade pivot shift or revision ACL reconstruction as well as a persistent anterolateral rotatory instability following anatomic ACL reconstruction.

FRET-based cyanine probes for monitoring ligation reactions and their applications to mechanistic studies and catalyst screening.

There is an ever-increasing need to design better methods to selectively connect two molecules under mild aqueous conditions on a small scale. The process of finding such methods significantly relies on the employment of an appropriate assay. We report here a modular FRET-based assay to monitor such reactions and illustrate how the assay is used to monitor two particular reactions: native chemical ligation (NCL) and oxime ligation. For both reactions we show that by employing appropriately designed probes FRET measurements could be used to monitor the reaction's progress. We additionally demonstrate the usefulness of the developed probe system to study the mechanisms of the ligation reactions, for example, in monitoring the formation of a trimeric intermediate in the NCL reaction. Finally, we demonstrate that FRET measurements conducted in our system allow the quantification of the reaction yield and we show the application of our FRET-based assay to catalyst screening for the oxime ligation.

Exercise training normalizes mitochondrial respiratory capacity within the striatum of the R6/1 model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive cell loss in the striatum and cerebral cortex, leading to a decline in motor control and eventually death. The mechanisms promoting motor dysfunction are not known, however loss of mitochondrial function and content has been observed, suggesting that mitochondrial dysfunction may contribute to HD phenotype. Recent work has demonstrated that voluntary wheel running reduces hindlimb clasping in the R6/1 mouse model of HD, which we hypothesized may be due to preservation of mitochondrial content with exercise. Therefore, we investigated the role of chronic exercise training on preventing symptom progression and the loss of mitochondrial content in HD. Exercising R6/1 mice began training at 7 wks of age and continued for 10 or 20 wks. At 17 wks of age, R6/1 mice displayed a clasping phenotype without showing changes in mitochondrial respiration or protein content in either the cortex or striatum, suggesting mitochondrial dysfunction is not necessary for the progression of symptoms. At 27 wks of age, R6/1 mice demonstrated no additional changes in mitochondrial content or respiration within the cortex, but displayed loss of protein in complexes I and III of the striatum, which was not present in exercise-trained R6/1 mice. Mitochondrial respiration was also elevated in the striatum of R6/1 mice at 27 wks, which was prevented with exercise training. Together, the present study provides evidence that mitochondrial dysfunction is not necessary for the progression of hindlimb clasping in R6/1 mice, and that exercise partially prevents changes in mitochondrial content and function that occur late in HD.

Functional assessments for decision-making regarding return to sports following ACL reconstruction. Part II: clinical application of a new test battery.

PURPOSE: The purpose of this study was to utilize a novel functional test system to facilitate determining the time of return to sports following ACL reconstruction. METHODS: Sixty-nine patients with unilateral ACL reconstruction were included in this pilot study. All the patients performed a standardized test battery consisting of one- and two-legged stability tests, counter movement jumps, speedy jumps, plyometric jumps and a quick feed test. The first test was administered on average 170.7 ± 75.1 days post-operatively, and the retest was administered on average 239.1 ± 79.7 days post-operatively. The values of the subtests were compared with the normative data of healthy gender- and age-matched controls to determine the functional capacities of patients following ACL reconstruction. RESULTS: After the first and second test, 15.9 and 17.4 % of the patients met the criteria for a "return to non-competitive sports". One patient fulfilled the criteria for a "return to competitive sports" after the second test battery. The most limiting factor was a poor LSI value of <90 % if the dominant leg was involved and <80 % if the non-dominant leg was involved. CONCLUSION: This test battery demonstrates that, in terms of neuromuscular abilities, most patients, compared to healthy controls, are most likely not ready for a safe return to sports, even 8 months post-operatively. This should be considered in the future to determine when it is safe to return to sports and should avoid a premature return to competitive sports. LEVEL OF EVIDENCE: III.

Challenges in modelling the reaction chemistry of interstellar dust.

Studies aiming to understand the physicochemical properties of interstellar dust and the chemical reactions that occur on and in it have traditionally been the preserve of astronomical observation and experimental attempts to mimic astronomically relevant conditions in the laboratory. Increasingly, computational modelling in its various guises is establishing a complementary third pillar of support to this endeavour by providing detailed insights into the complexities of interstellar dust chemistry. Inherently, the basis of computational modelling is to be found in the details (e.g. atomic structure/composition, reaction barriers) that are difficult to probe accurately from observation and experiment. This bottom-up atom-based theoretical approach, often itself based on deeper quantum mechanical principles, although extremely powerful, also has limitations when systems become too large or complex. In this Perspective, after first providing a general background to the current state of observational-based knowledge, we introduce a number of computational modelling methods with reference to recent state-of-the-art studies, in order to highlight the capabilities of such approaches in this field. Specifically, we first outline the use of computational chemistry methods for dust nucleation, structure, and individual reactions on bare and icy dust surfaces. Later, we review kinetic modelling of networks of reactions relevant to dust chemistry and how to take into account quantum tunnelling effects in the low temperature reactions in the interstellar medium. Finally, we point to the future challenges that need to be overcome for computational modelling to provide even more detailed and encompassing perspectives on the nature and reaction chemistry of interstellar dust.

Omega-3 supplementation alters mitochondrial membrane composition and respiration kinetics in human skeletal muscle.

Studies have shown increased incorporation of omega-3 fatty acids into whole skeletal muscle following supplementation, although little has been done to investigate the potential impact on the fatty acid composition of mitochondrial membranes and the functional consequences on mitochondrial bioenergetics. Therefore, we supplemented young healthy male subjects (n = 18) with fish oils [2 g eicosapentaenoic acid (EPA) and 1 g docosahexanoic acid (DHA) per day] for 12 weeks and skeletal muscle biopsies were taken prior to (Pre) and following (Post) supplementation for the analysis of mitochondrial membrane phospholipid composition and various assessments of mitochondrial bioenergetics. Total EPA and DHA content in mitochondrial membranes increased (P < 0.05) ∼450 and ∼320%, respectively, and displaced some omega-6 species in several phospholipid populations. Mitochondrial respiration, determined in permeabilized muscle fibres, demonstrated no change in maximal substrate-supported respiration, or in the sensitivity (apparent Km) and maximal capacity for pyruvate-supported respiration. In contrast, mitochondrial responses during ADP titrations demonstrated an enhanced ADP sensitivity (decreased apparent Km) that was independent of the creatine kinase shuttle. As the content of ANT1, ANT2, and subunits of the electron transport chain were unaltered by supplementation, these data suggest that prolonged omega-3 intake improves ADP kinetics in human skeletal muscle mitochondria through alterations in membrane structure and/or post-translational modification of ATP synthase and ANT isoforms. Omega-3 supplementation also increased the capacity for mitochondrial reactive oxygen species emission without altering the content of oxidative products, suggesting the absence of oxidative damage. The current data strongly emphasize a role for omega-3s in reorganizing the composition of mitochondrial membranes while promoting improvements in ADP sensitivity.

The impact of recent advances in laboratory astrophysics on our understanding of the cosmos.

An emerging theme in modern astrophysics is the connection between astronomical observations and the underlying physical phenomena that drive our cosmos. Both the mechanisms responsible for the observed astrophysical phenomena and the tools used to probe such phenomena-the radiation and particle spectra we observe-have their roots in atomic, molecular, condensed matter, plasma, nuclear and particle physics. Chemistry is implicitly included in both molecular and condensed matter physics. This connection is the theme of the present report, which provides a broad, though non-exhaustive, overview of progress in our understanding of the cosmos resulting from recent theoretical and experimental advances in what is commonly called laboratory astrophysics. This work, carried out by a diverse community of laboratory astrophysicists, is increasingly important as astrophysics transitions into an era of precise measurement and high fidelity modeling.

Millimeter-wave time-resolved studies of HCO+-H2 inelastic collisions.

A novel ion cell has been constructed for the purpose of studying rotationally inelastic collisions involving truly thermal molecular ions at low temperatures. With this ion cell, time-resolved double resonance (pump-probe) spectroscopic experiments have been performed to determine the cross sections for relaxation of the J = 2 state of HCO+ in collisions with normal-H2 at temperatures around 40 and 77 K. The HCO+ is pumped through the J = 2<--1 transition and probed via the J = 3<--2 transition. The cross sections at the lower temperature are slightly below those predicted by the simple Langevin theory, while those at the higher temperature are in good agreement with this theory.

[Symptomatic Langerhans-cell-histiocytosis of the cervical spine in a child: case report]. / Die symptomatische Langerhanszell-Histiozytose der kindlichen HWS: Eine Falldarstellung.

We report on a six year old female presented with a painful torticollis and a hemidysaesthesia caused by destruction of the third cervical vertebra and a paravertebral soft-tissue mass. At diagnostic routine finally a biopsy gives the diagnosis of Langerhans cell histiocytosis. In a second open approach the destructed vertebral body was replaced by a precisely adjusted autologous bone interponate and the patient was maintained in halo vest immobilisation. The outcome is described and an overview of the current literature is given.

Apolipoprotein E4 promotes the early deposition of Abeta42 and then Abeta40 in the elderly.

The apolipoprotein Eepsilon4 allele (ApoEepsilon4) is associated with a selective increase in deposition of the 40-amino acid form of the beta-amyloid peptide (Abeta40) in endstage Alzheimer's disease. To determine how apoE genotype affects the early events in beta-amyloid pathogenesis, we analyzed the medial temporal lobes of 244 elderly persons who were not clinically demented using antibodies selective for the C termini of Abeta40 and Abeta42. We found that: (1) the number of both Abeta42- and Abeta40-positive senile plaques increase with age; (2) Abeta42 appears at younger ages, and in more amyloid deposits, than does Abeta40 in all ApoE groups; (3) when compared at similar ages, older persons with ApoEepsilon4 are more likely to have Abeta42- and Abeta40-immunoreactive deposits than are persons without ApoEepsilon4; (4) Abeta40-containing plaques arise at least a decade later than do Abeta42 plaques, and are seldom found in the medial temporal lobe of older persons lacking ApoEepsilon4; and (5) in the absence of overt Alzheimer's disease, cerebral amyloid angiopathy is rare in the elderly, but in our sample was significantly augmented in ApoEepsilon4 homozygotes. We conclude that ApoEepsilon4 hastens the onset of Abeta42 deposition in the senescent brain, which in turn fosters the earlier evolution of fibrillar, Abeta40-positive plaques, thereby increasing the risk of Alzheimer's disease.

Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma.

PURPOSE: Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology. MATERIALS AND METHODS: We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease. RESULTS: The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p < 0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm. CONCLUSIONS: von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.

Intravascular lymphoma presenting as symmetric polyarthritis.

Intravascular lymphoma (IVL) is an uncommon neoplastic disorder characterized by monoclonal intravascular expansion of lymphoid cells. Occlusion of small vessels in various organ systems probably accounts for the broad clinical spectrum of this type of lymphoma, which can closely mimic a variety of diseases, especially vasculitic disorders, and thus lead to delayed clinical diagnosis. This is the first report of a patient who presented with a predominant symptom of symmetric polyarthritis accompanied by fever. While her initial systemic symptoms, such as fever, improved rapidly after initiation of corticosteroid therapy, the response of the polyarthritic joint manifestations was only transient. The patient died of progressive lung involvement and was diagnosed as having IVL by histologic analysis of tissue samples obtained postmortem.

Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly.

To evaluate the influence of the apolipoprotein E (ApoE) epsilon4 allele on the age at which Alzheimer-like lesions appear in the brain, we analyzed the degree of cerebral beta-amyloidosis and neurofibrillary tangle formation in the hippocampal formation and adjacent cortical areas 28, 27, and 36 of persons who had died between the ages of 50 and 93 years and who had shown no signs of clinical dementia. The occurrence of the three common polymorphisms of the ApoE gene in this sample of 147 routine autopsy cases from eastern Germany was comparable to previously reported values in European and North American populations: ApoEepsilon2/2, 0.7%; ApoEepsilon2/3, 14.3%; ApoEepsilon2/4, 4.1%; ApoEepsilon3/3, 56.5%; ApoEepsilon3/4, 22.4%; and ApoEepsilon4/4, 2.0%. Nondemented persons carrying the ApoEepsilon4 allele were significantly more likely to have senile plaques, diffuse amyloid deposits, cerebrovascular amyloid, and neurofibrillary tangles than were those lacking E4. Comparing the two largest ApoE subgroups, ApoEepsilon3/3 and ApoEepsilon3/4, the relative increase in the occurrence of beta-amyloid in the epsilon3/4 group was evident by the mid-60s, with the relative increase in neurofibrillary tangles in this group emerging slightly earlier. The ApoEepsilon2 allele appears to delay the appearance of the lesions somewhat. We conclude that ApoEepsilon4 promotes the early appearance of beta-amyloid and neurofibrillary tangles in the elderly and that the increased frequency of these lesions is related to the higher risk of Alzheimer disease in persons bearing the ApoEepsilon4 allele.

Generation of effective cancer vaccines genetically engineered to secrete cytokines using adenovirus-enhanced transferrinfection (AVET).

Cancer vaccines are based on the concept that tumors express novel antigens and thus differ from their normal tissue counterparts. Such putative tumor-specific antigens should be recognizable by the immune system. However, malignant cells are of self origin and only poorly immunogenic, which limits their capability to induce an anticancer immune response. To overcome this problem, tumor cells have been isolated, genetically engineered to secrete cytokine gene products and administered as cancer vaccines. We used adenovirus-enhanced transferrinfection (AVET), which allows high-level transient transgene expression, to introduce cytokine gene expression vectors into murine melanoma cells. The efficiency of AVET makes laborious selection and cloning procedures obsolete. We administered such modified tumor cells as cancer vaccines to syngeneic animals and investigated their impact on the induction of anticancer immunity. We found that IL-2 or GM-CSF gene-transfected murine melanoma cells are highly effective vaccines. Both of these cytokine-secreting vaccines cured 80% of animals which bore a subcutaneous micrometastasis prior to treatment, and induced potent antitumor immunity. The generation of antitumor immunity by these cytokine-secreting vaccines requires three different steps: (1) tumor antigen uptake and processing by antigen-presenting cells (APCs) at the site of vaccination; (2) migration of these APCs into the regional lymph nodes where T-cell priming occurs; (3) recirculation of specific, activated T-cells that recognize distinct tumor load and initiate its elimination. Extending our previously reported studies, we have now comprehensively analysed the requirements for effective antitumor vaccination in animals. This may also become the basis for treatment of human cancer patients.

The rate of the reaction between CN and C2H2 at interstellar temperatures.

The rate coefficient for the important interstellar reaction between CN and C2H2 has been calculated as a function of temperature between 10 and 300 K. The potential surface for this reaction has been determined through ab initio quantum chemical techniques; the potential exhibits no barrier in the entrance channel but does show a small exit channel barrier, which lies below the energy of reactants. Phase-space calculations for the reaction dynamics, which take the exit channel barrier into account, show the same unusual temperature dependence as determined by experiment, in which the rate coefficient at first increases as the temperature is reduced below room temperature and then starts to decrease as the temperature drops below 50-100 K. The agreement between theory and experiment provides strong confirmation that the reaction occurs appreciably at cool interstellar temperatures.